ALMS1

ALMS1 is a human gene that encodes the ALMS1 protein, a large centrosomal protein thought to play a role in the formation and function of cilia. The protein localizes predominantly to the centrosome and to basal bodies of primary cilia in many tissues. While the full range of its functions is not completely understood, ALMS1 is widely regarded as a ciliopathy-associated protein involved in ciliogenesis, centrosome function, and intracellular trafficking, with effects on signaling pathways that depend on ciliary activity.

Pathogenic variants in ALMS1 cause Alström syndrome, a rare autosomal recessive disorder. The condition is a systemic ciliopathy with childhood onset features including cone-rod dystrophy and progressive vision loss, sensorineural hearing loss, obesity and insulin resistance, type 2 diabetes, cardiomyopathy, hepatic and renal dysfunction, and progressive multiorgan degeneration. Diagnosis relies on clinical assessment and confirmation by sequencing showing biallelic pathogenic variants in ALMS1.

Mutations described in ALMS1 include truncating frameshift and nonsense changes, splice-site mutations, and missense variants; most mutations disrupt protein function or localization. In animal and cellular models, loss of ALMS1 leads to defects in cilia, altered cell signaling, and metabolic disturbances that mirror aspects of the human disease.

Research uses mouse and zebrafish models to study ALMS1 function and ciliopathy mechanisms, with the aim of understanding pathogenesis and identifying potential therapies for Alström syndrome.